An ERG and OCT study of neuronal ceroid lipofuscinosis CLN2 Battens retinopathy

Dorothy A Thompson,Robert H Henderson,Oliver R Marmoy,Siân E Handley,Paul Gissen

doi:10.1038/s41433-021-01594-y

Dorothy A Thompson, Robert H Henderson + Show 3 more

Open Access

https://doi.org/10.1038/s41433-021-01594-y

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Abstract

BackgroundLate infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood. The natural history of motor and language regression is used to monitor the efficacy of CNS treatments. Less is known about CLN2 retinopathy. Our aim is to elaborate the nature, age of onset, and symmetry of CLN2 retinopathy using visual electrophysiology and ophthalmic imaging.Subjects and methodsWe reviewed 22 patients with genetically confirmed CLN2 disease; seventeen showing classical and five atypical disease. Flash electroretinograms (ERGs), flash and pattern reversal visual evoked potentials (VEPs), recorded from awake children were collated. Available fundus images were graded, optical coherence tomography (OCT) central subfoveal thickness (CST) measured, and genotype, age, clinical vision assessment and motor language grades assembled.ResultsERGs show cone/rod system dysfunction preceded by localised macular ellipsoid zone disruption on OCT from 4.8 years. Electroencephalogram (EEG) time-locked spikes confounded both pattern 6/17 (35%) and flash VEPs 12/16 (75%). Paired right eye (RE) and left eye (LE) ERG amplitudes did not differ significantly for each flash stimulus at the p 0.001 level, Wilcoxon ranked signed test. Cone ERGs show a functional deficit before CST thinning in classical disease. Optomap hyper fundus autofluorescence (FAF) at the fovea was noted in three patients with normal ERGs. The oldest patient showed an ovoid aggregate above the external limiting membrane at the fovea, which did not affect the PERG.ConclusionERG findings in CLN2 retinopathy show symmetrical cone-rod dysfunction, from 4y10m in this series, but a broad range of ages when ERG function is preserved.

Highlights

Late infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood
Batten disease is a collective description for all forms of neuronal ceroid lipofuscinosis (NCL) [1, 2]
Flash skin ERG, pattern visual evoked potentials (VEPs) and flash VEP were carried out in awake children using techniques developed at Great Ormond Street Hospital for Children (GOSH)

Summary

Introduction

Late infantile neuronal ceroid lipofuscinosis (CLN2 Batten disease) is a rare, progressive neurodegenerative disease of childhood. Our aim is to elaborate the nature, age of onset, and symmetry of CLN2 retinopathy using visual electrophysiology and ophthalmic imaging. Available fundus images were graded, optical coherence tomography (OCT) central subfoveal thickness (CST) measured, and genotype, age, clinical vision assessment and motor language grades assembled. Results ERGs show cone/rod system dysfunction preceded by localised macular ellipsoid zone disruption on OCT from 4.8 years. Cone ERGs show a functional deficit before CST thinning in classical disease. Conclusion ERG findings in CLN2 retinopathy show symmetrical cone-rod dysfunction, from 4y10m in this series, but a broad range of ages when ERG function is preserved. Batten disease is a collective description for all forms of neuronal ceroid lipofuscinosis (NCL) [1, 2].

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